DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity.

C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein C-mannosylation are not yet fully understood, especially in tumor progression. Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells, enabling the tumors to form matrix-embedded vasculogenic structures, containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors. In this study, we focused on DPY19L3, a C-mannosyltransferase, and aimed to unravel its role in VM. Knockout of DPY19L3 inhibited the formation of VM in HT1080 human fibrosarcoma cells. Re-expression of wild-type DPY19L3 recovered VM formation; however, DPY19L3 isoform2, an enzymatic activity-defect mutant, did not restore it, suggesting that the C-mannosyltransferase activity of DPY19L3 is crucial to its function. Furthermore, the knockdown of DPY19L3 in MDA-MB-231 breast cancer cells hindered its network formation ability. Altogether, our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of C-mannosylation in oncogenesis.

Peripheral Arterial Disease in Women: The Gender Effect.

Peripheral arterial disease (PAD) is a common atherosclerotic disease approximately affecting 8.5 million Americans above age 40 and is associated with significant functional impairment, morbidity and mortality from both cardiovascular and non-cardiovascular causes. PAD has increasing prevalence in females contrary to previous findings. Compared to men, women with PAD are more asymptomatic or have atypical symptoms. Women with PAD have increased quality of life impairment, increased risk of depression and increased cardiovascular mortality. The intent of this review is to provide an update on gender differences in PAD that can help in timely diagnosis and appropriate management through intensive cardiovascular risk factor modification, exercise program and guideline directed therapy to improve cardiovascular outcomes.

The Incidence, Risk Factors, and Chronobiology of Acute Myocardial Infarction Ten Years After Hurricane Katrina.

OBJECTIVE: The purpose of this study was to investigate the 10-year impact of Hurricane Katrina on the incidence of acute myocardial infarction (AMI) along with contributing risk factors and any alteration in chronobiology of AMI. METHODS: A single-center, retrospective, comparison study of AMI incidence was performed at Tulane University Health Sciences Center from 2 years before Hurricane Katrina to 10 years after Hurricane Katrina. A 6-year, pre-Katrina and 10-year, post-Katrina cohort were also compared according to pre-specified demographic, clinical, and chronobiological data. RESULTS: AMI incidence increased from 0.7% (150/21,079) to 2.8% (2,341/84,751) post-Katrina (P<0.001). The post-Katrina cohort had higher rates of coronary artery disease (36.4% vs. 47.9%, P=0.01), diabetes mellitus (31.3% vs. 39.9%, P=0.04), hyperlipidemia (45.4% vs. 59.3%, P=0.005), smoking (34.4% vs. 53.8%, P<0.001), drug abuse (10.2% vs. 15.4%, P=0.02), psychiatric illness (6.7% vs. 14.9%, P<0.001), medication non-adherence (7.3% vs. 15.3%, P<0.001), and lack of employment (7.2% vs. 16.4%, P<0.001). The post-Katrina group had increased rates of AMI during nights (29.8% vs. 47.8%, P<0.001) and weekends (16.1% vs. 29.1%, P<0.001). CONCLUSIONS: Even 10 years after the storm, Hurricane Katrina continues to be associated with increased incidence of AMI, higher prevalence of traditional cardiovascular and psychosocial risk factors, and an altered chronobiology of AMI toward nights and weekends. (Disaster Med Public Health Preparedness. 2019;13:217-222).

Revascularization of Left Main Coronary Artery.

Left main coronary artery (LMCA) disease affect 5-7% of patient undergoing coronary angiography and is associated with multivessel CAD in 70% of the cases. Untreated significant LMCA disease is associated with significant mortality and morbidity. CABG is the traditional therapy for revascularization in LMCA disease. PCI is a reasonable alternative mainly in patients with high surgical risk or other specific factors. Drug-eluting stents, improved antiplatelet therapeutic options, atherectomy techniques, IVUS-guidance and improved operator experience have all contributed to the observed improvement in clinical outcomes. Given the large number of variables involved in deciding between PCI and CABG, a heart team should make decisions regarding revascularization of LMCA disease.

Current concepts in the management of stable ischemic heart disease and acute coronary syndrome in patients with hemophilia.

Coronary artery disease (CAD), including stable ischemic heart disease (SIHD) and acute coronary syndrome (ACS), remains the leading cause of death in the US and one of the primary modalities used in the treatment of CAD is percutaneous coronary intervention (PCI). Despite the potential benefits of PCI in high risk CAD patients, the risk of hemorrhage presents a dilemma in the treatment of patients with hemophilia A and B. In an attempt to provide guidance on the management of SIHD and ACS in patients with hemophilia, we present the case of a patient with moderate hemophilia B and ACS who subsequently underwent PCI followed by a review of the associated literature.

Combined Radial and Femoral Access Strategy and Radial-Femoral Rendezvous in Patients With Long and Complex Iliac Occlusions.

We present cases of complex, calcified iliac occlusive disease revascularized via a combined radial-femoral access strategy. Through a 6-French, 125-cm transradial guiding catheter, antegrade guidewires and catheters are advanced into the iliac occlusion, while retrograde devices are advanced transfemorally. The transradial and transfemoral channels communicate, allowing the devices to cross the occlusion into the true lumen (radial-femoral antegrade-retrograde rendezvous).

Safety and efficacy of everolimus-eluting bioresorbable vascular scaffolds versus durable polymer everolimus-eluting metallic stents assessed at 1-year follow-up: A systematic review and meta-analysis of studies.

BACKGROUND: The Absorb bioresorbable vascular scaffold (BVS) was developed to address long-term safety issues of metallic drug-eluting stents. However, it may be associated with an increased event risk during the first year. METHODS: A systematic literature search was performed (in MEDLINE/PubMed, Cochrane CENTRAL, EMBASE, and scientific meeting abstracts) to identify studies that compared BVS and cobalt-chromium durable polymer everolimus-eluting stents (EES). For randomized clinical trials and non-randomized propensity score matched studies that reported 1-year outcome data, fixed/random-effects models were used to generate pooled estimates of outcomes, presented as odds ratios (OR) with 95%-confidence intervals (CI). RESULTS: The 1-year follow-up data of 6 trials with 5588 patients were analyzed. A device-oriented composite endpoint (DOCE - cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR)) was reached by 308 BVS or EES patients (195/3253 vs. 113/2315). Meta-analysis showed that patients who received BVS had an increased risk of MI (4.3% vs. 2.3%; OR:1.63, 95%-CI: 1.18-2.25, p<0.01) and definite-or-probable scaffold thrombosis (1.3% vs. 0.6%; OR:2.10, 95%-CI: 1.13-3.87, p=0.02). However, there was no significant between-group difference in risk of DOCE (6.0% vs. 4.9%; OR:1.19, 95%-CI: 0.94-1.52, p=0.16), cardiac death (0.8% vs. 0.7%; OR:1.14, 95%-CI: 0.54-2.39, p=0.73), or TLR (2.5% vs. 2.5%; OR: 0.98, 95%-CI:0.69-1.40, p=0.92). CONCLUSIONS: During the first year of follow-up, patients treated with BVS had a higher incidence of MI and scaffold thrombosis. The risk of DOCE was not significantly different. As BVS may pay off later, future robust data on long-term clinical outcome will be of paramount importance.

Using Discrete Event Simulation to Model the Economic Value of Shorter Procedure Times on EP Lab Efficiency in the VALUE PVI Study.

BACKGROUND: The VALUE PVI study demonstrated that atrial fibrillation (AF) ablation procedures and electrophysiology laboratory (EP lab) occupancy times were reduced for the cryoballoon compared with focal radiofrequency (RF) ablation. However, the economic impact associated with the cryoballoon procedure for hospitals has not been determined. OBJECTIVE: Assess the economic value associated with shorter AF ablation procedure times based on VALUE PVI data. METHODS AND RESULTS: A model was formulated from data from the VALUE PVI study. This model used a discrete event simulation to translate procedural efficiencies into metrics utilized by hospital administrators. A 1000-day period was simulated to determine the accrued impact of procedure time on an institution's EP lab when considering staff and hospital resources. The simulation demonstrated that procedures performed with the cryoballoon catheter resulted in several efficiencies, including: (1) a reduction of 36.2% in days with overtime (422 days RF vs 60 days cryoballoon); (2) 92.7% less cumulative overtime hours (370 hours RF vs 27 hours cryoballoon); and (3) an increase of 46.7% in days with time for an additional EP lab usage (186 days RF vs 653 days cryoballoon). Importantly, the added EP lab utilization could not support the time required for an additional AF ablation procedure. CONCLUSIONS: The discrete event simulation of the VALUE PVI data demonstrates the potential positive economic value of AF ablation procedures using the cryoballoon. These benefits include more days where overtime is avoided, fewer cumulative overtime hours, and more days with time left for additional usage of EP lab resources.

Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III-V, and ESRD.

Patients with chronic kidney disease (CKD) are three times more likely to have myocardial infarction (MI) and suffer from increased morbidity and higher mortality. Traditional and unique risk factors are prevalent and constitute challenges for the standard of care. However, CKD patients have been largely excluded from clinical trials and little evidence is available to guide evidence-based treatment of coronary artery disease in patients with CKD. Our objective was to assess whether a difference exists in the management of MI (ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction) among patients with normal kidney function, CKD stage III-V, and end-stage renal disease (ESRD) patients. We conducted a retrospective cohort study on patients admitted to Staten Island University Hospital for the diagnosis of MI between January 2005 and December 2012. Patients were assigned to one of three groups according to their kidney function: Data collected on the medical management and the use of statins, platelet inhibitors, beta-blockers, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers were compared among the three cohorts, as well as medical interventions including: catheterization and coronary artery bypass graft (CABG) when indicated. Chi-square test was used to compare the proportions between nominal variables. Binary logistic analysis was used in order to determine associations between treatment modalities and comorbidities, and to account for possible confounding factors. Three hundred and thirty-four patients (mean age 67.2±13.9 years) were included. In terms of management, medical treatment was not different among the three groups. However, cardiac catheterization was performed less in ESRD when compared with no CKD and CKD stage III-V (45.6% vs 74% and 93.9%) (P<0.001). CABG was performed in comparable proportions in the three groups and CABG was not associated with the degree of CKD (P=0.078) in binary logistics regression. Cardiac catheterization on the other hand carried the strongest association among all studied variables (P<0.001). This association was maintained after adjusting for other comorbidities. The length of stay for the three cohorts (non-CKD, CKD stage III-V, and ESRD on hemodialysis) was 16, 17, and 15 days, respectively and was not statistically different. Many observations have reported discrimination of care for patients with CKD considered suboptimal candidates for aggressive management of their cardiac disease. In our study, medical therapy was achieved at high percentage and was comparable among groups of different kidney function. However, kidney disease seems to affect the management of patients with acute MI; percutaneous coronary angiography is not uniformly performed in patients with CKD and ESRD when compared with patients with normal kidney function.

Cardiac Adrenergic Nervous System and Left Ventricular Remodeling.

Heightened cardiac adrenergic nervous system (ANS) activity and progression of left ventricular (LV) remodeling are temporally related in patients with systolic heart failure. Whether cardiac ANS activation directly contributes to or merely accompanies LV remodeling remains an unresolved issue. Human and experimental data that directly link cardiac ANS activation to LV remodeling and worsening heart failure are first reviewed, including cardiac norepinephrine spillover. Alterations of beta adrenergic receptor signaling pathways are then addressed with emphasis on the mechanisms that may mediate the beneficial effect of beta adrenergic receptor blockade on LV remodeling. Lastly, alternative approaches to beta adrenergic receptor blockade for lessening cardiac ANS activation and reversing cardiac ANS-induced LV remodeling are discussed. A large body of work now links LV remodeling to cardiac ANS activation. However, the precise mechanisms that link cardiac ANS activation to LV remodeling are still to be fully understood. Fully understanding of these mechanisms may uncover new therapeutic approaches.

Major complications of cryoballoon catheter ablation for atrial fibrillation and their management.

Atrial fibrillation (AF) is the most common symptomatic and sustained cardiac arrhythmia. It affects approximately 2-3 million people in the USA alone with an increased incidence and prevalence worldwide. It is associated, in addition to worsening quality of life, with increased morbidity and mortality especially in poorly controlled AF, affecting mostly those older than 65 years of age. Radiofrequency ablation was found to be a good strategy for focal isolation of pulmonary veins triggering from the vulnerable atrial substrate but is a time-consuming procedure and carries the risk of multiple complications like tamponade which could be fatal, atrioesophageal fistula and local thrombus formation at the site of ablation. Cryoballoon ablation with pulmonary vein isolation has emerged in the past few years as a breakthrough novel technology for the treatment of drug-refractory AF. It is a relatively simple alternative for point-by-point radiofrequency ablation of paroxysmal AF and is associated with fewer incidences of fatal complications such as cardiac perforation. As experience with this new tool accumulates, the field faces new challenges in the form of rare compilations including gastroparesis, phrenic nerve palsy, atrioesophageal fistula, pulmonary vein stenosis, thromboembolism pericardial effusion, and tamponade.

Acute ST-segment elevation myocardial infarction in a young patient with essential thrombocythemia: a case with long-term follow-up report.

Essential thrombocythemia (ET) is a neoplastic proliferation of mature myeloid cells - in particular, megakaryocytes - leading to persistently elevated platelet count. Usual clinical presentation is related to an increase in the risk of hemorrhage and/or thrombosis. Management of ET consists of antiplatelet therapies - mainly aspirin and cytoreductive therapies. Coronary involvement in patients with ET is rare. The optimal treatment strategies for ET patients presenting with acute myocardial infarction remains unclear. Acute interventions like intracoronary thrombolytic therapy, angioplasty, and coronary-artery bypass grafting have been reported in such patients. However, several questions remain unanswered about the acute and long-term management of these patients. Herein, we report the case of a 47-year-old female who presented with acute myocardial infarction as the first clinical sign of ET, and also present the long-term follow-up of this patient.

Comparison of resource utilization of pulmonary vein isolation: cryoablation versus RF ablation with three-dimensional mapping in the Value PVI Study.

BACKGROUND: Point-to-point focal radiofrequency (RF) catheter ablation for aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is the traditional method for treating symptomatic drug-resistant paroxysmal AF (PAF) when an ablation procedure is warranted. More recently, pulmonary vein isolation (PVI) using the cryoballoon has been demonstrated to be safe and effective (STOP AF clinical trial). Currently, two small studies have reviewed the procedural efficiency when comparing cryoballoon to focal RF catheter ablation procedures; however, no multicenter study has yet reported on this comparison of the two types of ablation catheters. METHODS: A multicenter retrospective chart extraction and evaluation was conducted at seven geographically mixed cardiac care centers. The study examined procedural variables during ablation for PVI in PAF patients. RESULTS: In several procedural measurements, the two modalities were comparable in efficiencies, including: acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30% usage of adenosine after procedural testing. However, when compared to RF catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min). Additionally, when comparing the material usage of both cryoballoon and RF catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc) while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs 87%), and fewer transseptal punctures (1.5 vs 1.9). CONCLUSION: This study is the first United States multicenter examination to report the procedural comparisons between the cryoballoon and focal RF catheters when used for the treatment of PAF patients. In this hospital chart review study, potential advantages were found when operating the cryoballoon with regard to hospital resource allocation. There was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure.

A unique complication with use of the GuideLiner catheter in percutaneous coronary interventions and its successful management.

The "GuideLiner" is an easy-to-use catheter designed for deep seating in coronary arteries. The GuideLiner can be used to provide extra guidance support for equipment delivery during difficult coronary interventions or for coaxial alignment in tortuous vessels. There are a few GuideLiner-related complications reported in the literature, which include stent damage on advancement or on withdrawal, dissection, pressure dampening and ischemia, kinking of the balloon, and displacement of the GuideLiner catheter distal marker. We report another unique and previously unreported GuideLiner-related complication and its successful management. In our case, we experienced dislodgment of the distal cylinder of the GuideLiner from the push rod into the aortic root. The embolized cylinder was removed percutaneously using a novel approach without any complications.

Levamisole-contaminated cocaine: an emergent cause of vasculitis and skin necrosis.

The prevalence of cocaine adulterated with levamisole-induced vasculitis is increasing and physicians should be aware of this unique entity. There have been many reports of cutaneous vasculitis syndrome caused by cocaine which is contaminated with levamisole. Levamisole was used as an antihelminth drug and later was rescinded from use in humans due to adverse effects. Through this paper, we will report a 39-year-old crack cocaine user who presented with purpuric rash and skin necrosis of his ear lobes. Levamisole-induced vasculitis syndrome was suspected. A urine toxicology screen was positive for cocaine, opiates, and marijuana. Blood work revealed positive titres of ANA and p-ANCA, as well as anti-cardiolipin antibody. Biopsy taken from the left ear showed focal acute inflammation, chronic inflammation with thrombus formation, and extravasated blood cells. Treatment was primarily supportive with wound care.

Persistent thebesian vessels involving the right and left ventricles leading to coronary steal phenomena and ischemia.

We report an extremely rare case of thebesian vein microfistulae to both ventricles. A 65-year-old woman, with no major cardiovascular risk factors, presented with multiple episodes of chest pain. The resting electrocardiogram showed T-wave inversion in leads V(1) -V(4). A Dipyridamole myocardial perfusion imaging revealed large and severe inferior defect with complete reversibility. Coronary angiography showed no coronary artery disease. On contrast injection, an exaggerated capillary blush from the distal portions of the right and left coronary artery systems was seen in both ventricles, mimicking the image of ventriculography. This appearance suggests prominent thebesian vessels, a congenital communication between the coronaries and the two ventricles. The clinical relevance of these myocardial sinusoids is still not well established. Although the majority of these fistulas are small in size and with no clinical significance, they can rarely present with chest pain, cardiac arrhythmia, syncope, myocardial infarction, and/or pulmonary hypertension. These fistulae when excessive can cause significant shunting of blood to the ventricles, leading to coronary steal phenomena and ischemia. This phenomenon is facilitated by the low resistance in these microfistulae as opposed to the higher resistance in the normal coronary circulation. Due to the diffuse nature of these microfistulae, neither surgery nor transcatheter therapy is feasible. This condition can only be managed medically; however, it should be noted that vasodilator agents, such as nitrates, can worsen the coronary steal phenomenon. Our patient was treated with ranolazine with significant improvement in her symptoms, which was not reported previously. Multiple coronary artery microfistulae could be an underestimated condition of angina in patient with normal coronaries.

From right to left heart failure: an unexpected transition.

Right and left heart failure are very common clinical syndromes with close correlation. Right-sided or right ventricular heart failure usually occurs as a result of left-sided failure. We report a very rare case of transition from right heart failure due to pulmonary embolism, followed by its resolution, to left heart failure due to Tako-tsubo syndrome within 48 h of hospitalization.

Effects of proton pump inhibitors and electrolyte disturbances on arrhythmias.

Several case reports have been written regarding the relationship between the use of proton pump inhibitors (PPI) and hypomagnesemia. Some of these reported cases have electrocardiogram abnormalities where electrolytes deficiencies were the contributing factor for these events. This study investigates the correlation between different arrhythmias and the use of PPI and hypomagnesaemia incidence. Four-hundred and twenty-one patients admitted to the critical care unit with unstable angina, non-ST elevation myocardial infarction, and ST-elevation myocardial infarction were included in this study. One-hundred and eighty-four patients (43.8%) received PPI and 237 patients (51.16%) did not, magnesium levels were low (<1.8 mg/dL) in 95 patients (22.5%), and 167 patients (39.6%) developed arrhythmias. The P-values for the regression coefficient association for the use of PPI and the level of magnesium were P = 1.31e(-29) and P = 8e(-102), respectively. The P-values indicate that there is a statistically significant association between the PPI use, magnesium levels, and the occurrence of cardiovascular events, with a strong correlation factor of 0.817. Patients receiving PPIs should be followed closely for magnesium deficiency, especially if they experience acute cardiovascular events, because this may contribute to worsening arrhythmias and further complications.

Thrombus in Transit through Patent Foramen Ovale.

A thrombus in transit through a patent foramen ovale (PFO) with impending paradoxical embolism is an extremely rare event. Due to its transient nature, it is unable to identify the thrombus, and most of the cases have been reported at autopsy. We are reporting a case of thrombus straddling the foramen ovale which was diagnosed by echocardiography and treated surgically. Through this personal case, an exhaustive review of the literature was performed. There were 88 cases reported. We concluded that there is no medical consensus about the best option for treatment. Nevertheless, surgery, which is associated with fewer complications of recurrent embolic events than those of thrombolysis and anticoagulation, appeared to be the best approach in patients who are not at a high surgical risk. Anticoagulant treatment appears to be an acceptable therapeutic alternative to surgery, particularly in patients with comorbidities who are at high surgical risk and for patients with small PFO. Thrombolysis is linked to the highest mortality, which could be explained by the severity of the patient's initial presentation. In conclusion, and after the cumulative effects of these case reports, we propose a diagram consisting of the use of the three therapeutic options in the different clinical scenarios.